The proposed program uses approaches within the disciplines of neuroanatomy, neuropharmacology, neurophysiology, molecular biology, and developmental neurobiology to study 1) the ways in which the development of cortical connectivity and the actions of transmitters and modulators within cortical circuits interact to regulate excitability of those circuits and their constituent neurons, and 2) the disorders in those interactions that can lead to epileptogenesis. The specific project are: I: Regulation of neuronal excitability in chronic epiletogenesis; II: Development of local connections in cerebral cortex; and III: Functional development and modulation of callosal synapses. The techniques employed include use of in vitro cortical, callosal and thalamocortical slices for current and voltage clamp recordings with patch pipettes to obtain spontaneous and evoked whole cell currents; preparation of experimental microgyri; biophysical methods for analysis of currents; applicants of drugs and chemicals; recordings and intracellular filling of visualized neurons in ~thin~ slices and anatomic analysis of filled neurons; field potential recordings; organotypic cortical culture and neuronal transplantation; membrane stripe assays; orthograde and retrograde labelling; confocal microscopy; and use of chronic models of epilepsy in vitro. The long term goals of the Program are to provide a better understanding of the pathogenesis of epilepsy and insights that will lead to rational new approaches to the prevention and treatment of this disorder. The studies outlined also will contribute to our understanding of normal and abnormal cortical development, and regulation of cerebral excitability through the effects of functional connections, and specific transmitter systems.